1. Field of the Invention
The present invention relates to a method for diagnosing hypertension, and/or allergy, and/or hair loss, and/or liability for infection, of a human being, or a predisposition therefor; to a nucleic acid molecule coding for a human ClCKb protein comprising a genetic alteration at amino acid position 481 compared to the wild type, as well as for corresponding segments thereof; to a nucleic acid molecule which binds to the before-mentioned nucleic acid molecule under stringent conditions, as well as to a nucleic acid molecule which binds to that nucleic acid molecule; to a (poly)peptide encoded by the afore-mentioned nucleic acid molecules; to a method for identifying substances modulating activity of a peptide derived from ClCKb protein that is genetically altered at amino acid position 481 compared to the wild type; to a substance for modulating activity of a peptide derived from ClCKb protein that is genetically altered at amino acid position 481 compared to the wild type; to methods for preparing a pharmaceutical composition for treatment of hypertension, and/or allergy, and/or hair loss, and/or liability for infection; to pharmaceutical compositions; and to a method for treating a human being affected by hypertension, and/or allergy and/or hair loss, and/or liability for infection.
2. Related Prior Art
Methods of these afore-mentioned kinds in general are known in the art.
About 20% of the population of Western industrial nations are suffering from high blood pressure. Subsequent illnesses such as apoplectic stroke, cardiac infarction, renal insufficiency, and peripheral circulatory disorders belong to the most frequently causes of death. Up to now the cause for high blood pressure can be uncovered in less than 10% of the high blood pressure patients, as being an endocrine disorder (ca. 1%) or a kidney disease (ca. 7%). If no cause can be found, one speaks of an essential hypertension. If hypertension appears in a familial cumulative manner then evidence is given for the existence of genetic defects. Actually, up to now several monogenetic diseases leading to hypertension have been discovered.
For example, in the Liddle's syndrom a mutation of the renal Na+ channel ENaC has been identified which causes an increased activity of that channel (gain of function mutation); cf. Hansson J. H. et al. (1995), Nat Genet 11, 76–82; Lifton R. P. (1996), Science 272, 676–680; Schild L. et al. (1996), EMBO J 15, 2381–2387. In the so-called Gordon syndrome a mutation of a kinase leads to an overactivity of the renal NaCl co-transporter; Wilson F. H. et al. (2001), Science 293, 1107–1112. Mutations of the mineral corticoid receptors, Geller D. S. (1998), Nat Genet 19, 279–281, cf. Geller D. S. et al. (2000), Science 289, 119–123, or of the cortisole degradating enzyme 11-β-hydroxy steroid dehydrogenase, cf. Mune T. et al. (1995), Nat Genet 10, 394–399; Stewart P. M. et al. (1996), Lancet 347, 88–91, and the glucocortocoid remediable hypertension, Lifton R. P. et al. (1992), Nature 355, 262–265, Lifton R. P. et al. (1992), Nat Genet 2, 66–74, lead to hypertension via increased activity of ENaC. All of these diseases are extremely rare. An overview about the current knowledge concerning the genetics of rare forms of hypertension is given in Staessen et al. (2003), Lancet 361, 1629–1641.
On account of lacking of genetic information regarding widespread forms of hypertension up to now hypertension is usually diagnosed via blood pressure measurements, i.e. hemodynamometry, normally via the method according to Riva-Rocci.
This common method for diagnosing hypertension has several disadvantages. Firstly, blood pressure measurements, of course, give no information about the physiological and medical cause of a diagnosed hypertension. Secondly, because of lacking of knowledge about the cause of a diagnosed hypertension the basis for a goal-orientated therapy or prevention is not given. Thirdly, by common blood pressure measurements only an existing or acute hypertension will be identified, e.g. not a predisposition therefor.